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2015
Master Thesis
Titel
Engineering functionalized DNA nanostructures for biomedical applications
Abstract
In recent years, DNA nanotechnology has emerged into a fast-growing field that offers many applications in a wide range of areas. The unique possibility to manufacture self-assembled DNA nanostructures that can be spatially functionalized with biomolecules with single-nanometer resolution has led to great interest for medical applications. One idea is to use these types of structures as platforms for intelligent drug carriers because of their biodegradability, low toxicity and versatility. In doing so, effectiveness, stability as well as solubility of drugs could all be improved. On account of this, the design and fabrication of functionalized DNA nanostructures were investigated during the course of this master´s thesis in two separate projects: The first project, comprising the main part of this work, focused on the site-specific attachment of polyethylene glycol (PEG) to DNA origami structures. Six-helix bundle (6HB) structures formed by the DNA origami method were covalently PEGylated at specific locations on their surface, using approaches based on amine/NHS ester coupling and click chemistry. The most promising results were obtained using copper-free click chemistry as confirmed by agarose gel electrophoresis and transmission electron microscope (TEM) imaging. Surprisingly, AFM imaging was unable to resolve PEG coupling on the DNA origami structures, both in fluids and in air. Eventually, these types of structures could potentially operate as targeted vehicles for the transport of hydrophobic drugs displaying low solubility in blood due to their non-covalent interaction with PEG, and therefore may also be capable of improving the delivery of their cargo in therapeutic medicine. The second project dealt with a small (~7 nm) wireframe tetrahedron built from four DNA strands, a different and simpler kind of DNA nanostructure. Preliminary experiments exploring the modification with peptides resulted in promising findings which encourage continuation. A third topic in this work was realization of general experiments that contribute to more efficient syntheses of DNA origami. Notably, the focus lay on analysis of isothermal folding and purification of bacteriophages to obtain higher yields of correct folded DNA origami.
ThesisNote
Jena, Univ., Master Thesis, 2015
Author(s)
Beteiligt
Verlagsort
Jena